Although originally discovered inducing important biological functions in the nervous system, repulsive guidance molecule a (RGMa) has now been identified as a player in many other processes and diseases, including in myogenesis. RGMa is known to be expressed in skeletal muscle cells, from somites to the adult. Functional in vitro studies have revealed that RGMa overexpression could promote skeletal muscle cell hypertrophy and hyperplasia, as higher efficiency in cell fusion was observed. Here, we extend the potential role of RGMa during C2C12 cell differentiation in vitro. Our results showed that RGMa administrated as a recombinant protein during late stages of C2C12 myogenic differentiation could induce myoblast cell fusion and the downregulation of different myogenic markers, while its administration at early stages induced the expression of myogenic markers with no detectable morphological effects. We also found that RGMa effects on skeletal muscle hyperplasia are performed via neogenin receptor, possibly as part of a complex with other proteins. Additionally, we observed that RGMa-neogenin is not playing a role as an inhibitor of the BMP signalling in skeletal muscle cells. This work contributes to placing RGMa as a component of the mechanisms that determine skeletal cell fusion via neogenin receptor.

虽然最初发现在神经系统中诱导重要的生物学功能，但排斥引导分子 a (RGMa) 现在已被确定为许多其他过程和疾病的参与者，包括肌生成。已知 RGMa 在骨骼肌细胞中表达，从体节到成体。功能性体外研究表明，RGMa 过表达可促进骨骼肌细胞肥大和增生，因为观察到细胞融合效率更高。在这里，我们扩展了 RGMa 在体外 C2C12 细胞分化过程中的潜在作用。我们的结果表明 RGMa 在 C2C12 肌原性分化后期作为重组蛋白给药可诱导成肌细胞融合和不同肌原性标志物的下调，而其在早期阶段的给药诱导了生肌标志物的表达，而没有可检测到的形态学影响。我们还发现 RGMa 对骨骼肌增生的影响是通过新生素受体进行的，可能作为与其他蛋白质复合物的一部分。此外，我们观察到 RGMa-neogenin 在骨骼肌细胞中没有作为 BMP 信号传导的抑制剂发挥作用。这项工作有助于将 RGMa 作为通过新生素受体确定骨骼细胞融合的机制的一个组成部分。我们观察到 RGMa-neogenin 在骨骼肌细胞中没有作为 BMP 信号传导的抑制剂发挥作用。这项工作有助于将 RGMa 作为通过新生素受体确定骨骼细胞融合的机制的一个组成部分。我们观察到 RGMa-neogenin 在骨骼肌细胞中没有作为 BMP 信号传导的抑制剂发挥作用。这项工作有助于将 RGMa 作为通过新生素受体确定骨骼细胞融合的机制的一个组成部分。